Galectin-1 accelerates high-fat diet-induced obesity by activation of peroxisome proliferator-activated receptor gamma (PPARγ) in mice.
Galectin-1 accelerates high-fat diet-induced obesity by activation of peroxisome proliferator-activated receptor gamma (PPARγ) in mice.
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DOI：
10.1038/s41419-020-03367-z
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发表时间：
2021-01-11
影响因子：
9
通讯作者：
Chun KH
中科院分区：
文献类型：
--
作者：
Baek JH;Kim DH;Lee J;Kim SJ;Chun KH
作为凝集素家族的一员，半乳糖凝集素-1含有一个碳水化合物识别结构域（CRD）。在这里，我们研究了半乳糖凝集素-1是否调节脂肪形成和脂质积累。半乳糖凝集素-1 mRNA在代谢组织如肌肉和脂肪组织中高表达。高脂饮食（HFD）小鼠的白色脂肪组织（WATs）中半乳糖凝集素-1 mRNA表达高于正常脂肪饮食（NFD）小鼠。在脂肪细胞分化过程中，半乳糖凝集素-1的蛋白表达也增加。半乳糖凝集素-1沉默可抑制3T3-L1细胞的分化和脂肪生成因子（如PPARγ、C/EBPα、FABP4和FASN） mRNA和蛋白水平的表达。乳糖是一种与细胞外基质中半乳糖凝集素-1的CRD结合的抑制剂，不影响脂肪细胞的分化。半乳糖凝集素-1定位于3T3-L1细胞的多个细胞室。然而，我们发现DMI（地塞米松，甲基异丁基黄嘌呤，胰岛素）治疗增加了其核定位。有趣的是，半乳糖凝集素-1与PPARγ相互作用。半乳糖凝集素-1过表达导致PPARγ表达和转录活性增加。此外，我们制备了半乳糖凝集素-1敲除（Lgals1−/−）小鼠，并喂养60%的HFD。10周后，Lgals1−/−小鼠的体重和性腺WAT （gWAT）质量均低于野生型小鼠。Lgals1−/−小鼠的空腹血糖水平也低于野生型小鼠。此外，在Lgals1−/−小鼠的gWATs和肝组织中，脂肪生成基因显著下调。促炎细胞因子，如CCL2、CCL3、TNFα和F4/80，以及巨噬细胞标志物，在Lgals1−/−小鼠的gWATs和肝组织中也急剧下调。此外，Lgals1−/−小鼠棕色脂肪组织中与产热有关的基因表达升高。总的来说，半乳糖凝集素-1通过增加PPARγ的表达和激活，加剧了喂食HFD小鼠的肥胖。我们的研究结果表明半乳糖凝集素-1可能是一种潜在的治疗肥胖的靶点，需要进一步的临床应用研究。
Galectin-1 contains a carbohydrate-recognition domain (CRD) as a member of the lectin family. Here, we investigated whether galectin-1 regulates adipogenesis and lipid accumulation. Galectin-1 mRNA is highly expressed in metabolic tissues such as the muscle and adipose tissues. Higher mRNA expression of galectin-1 was detected in white adipose tissues (WATs) of mice that were fed a high-fat diet (HFD) than in those of mice fed a normal-fat diet (NFD). Protein expression of galectin-1 also increased during adipocyte differentiation. Galectin-1 silencing inhibited the differentiation of 3T3-L1 cells and the expression of lipogenic factors, such as PPARγ, C/EBPα, FABP4, and FASN at both mRNA and protein levels. Lactose, an inhibitor by the binding with CRD of galectin-1 in extracellular matrix, did not affect adipocyte differentiation. Galectin-1 is localized in multiple cellular compartments in 3T3-L1 cells. However, we found that DMI (dexamethasone, methylisobutylxanthine, insulin) treatment increased its nuclear localization. Interestingly, galectin-1 interacted with PPARγ. Galectin-1 overexpression resulted in increased PPARγ expression and transcriptional activity. Furthermore, we prepared galectin-1-knockout (Lgals1−/−) mice and fed a 60% HFD. After 10 weeks, Lgals1−/− mice exhibited lower body weight and gonadal WAT (gWAT) mass than wild-type mice. Fasting glucose level was also lower in Lgals1−/−mice than that in wild-type mice. Moreover, lipogenic genes were significantly downregulated in the gWATs and liver tissues from Lgals1−/− mice. Pro-inflammatory cytokines, such as CCL2, CCL3, TNFα, and F4/80, as well as macrophage markers, were also drastically downregulated in the gWATs and liver tissues of Lgals1−/− mice. In addition, Lgals1−/−mice showed elevated expression of genes involved in thermogenesis in the brown adipose tissue. Collectively, galectin-1 exacerbates obesity of mice fed HFD by increment of PPARγ expression and activation. Our findings suggest that galectin-1 could be a potential therapeutic target for obesity and needed further study for clinical application.
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影响因子：
3.7
作者：
D'Haene N;Sauvage S;Maris C;Adanja I;Le Mercier M;Decaestecker C;Baum L;Salmon I
通讯作者：
Salmon I
影响因子：
4
作者：
Akasheh, Rand T.;Pang, Jingbo;Fantuzzi, Giamila
通讯作者：
Fantuzzi, Giamila
影响因子：
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作者：
Kim SJ;Hwang JA;Ro JY;Lee YS;Chun KH
通讯作者：
Chun KH
影响因子：
12.4
作者：
通讯作者：
--
影响因子：
--
作者：
Parlee, Sebastian D.;Lentz, Stephen I.;Mori, Hiroyuki;MacDougald, Ormond A.
通讯作者：
MacDougald, Ormond A.